SCRIPPS STUDY LINKS SLEEPING PILLS, EARLY MORTALITY

Increased cancer risk is also found among steady sleep aid users

A new study by Scripps Clinic researchers may be a wake-up call for the millions of people who rely on sleeping pills to fall asleep. The report links the medications to a 4.6 times higher risk of death and a significant increase in cancer cases among regular pill users.

“What our study shows is that sleeping pills are hazardous to your health and might cause death by contributing to the occurrence of cancer, heart disease and other ailments,” said study author Dr. Daniel Kripke of the Scripps Clinic Viterbi Family Sleep Center in La Jolla.

The research looked at people who had been prescribed sleeping pills for an average of 2½ years and matched them with people of similar age, gender and health who received no sleeping aids. Over the 4½-year study, researchers found pill users had an average 4.6 times higher risk of death than nonusers.

The results were published Monday in the open-access online journal BMJ Open, a British peer-reviewed medical publication.

A combination of factors links higher rates of mortality and cancer to these drugs, researchers said.

“Some of the drugs may break chromosomes and (have been shown) to cause cancer in animals,” Kripke said. “We know they cause depression, and there’s a high rate of suicide in sleeping pill users.”

The drugs can cause gastroesophageal reflux disease, and regurgitated stomach acid may cause irritation to the esophagus, leading to infection, he said. Cancer of the esophagus and lung as well as lymphoma were significantly increased in sleeping pill users.

Sleep apnea often worsens with the use of sleeping pills, leading to hypertension and early mortality, according to the researchers.

“We also know that sleeping pills increase the risk of falls, especially in the elderly,” Kripke said. “Auto crashes (occur) more often with sleeping pill users.”

There have been 18 other studies showing the danger of these drugs, but this research is the first to show that eight of the most commonly used sedative-hypnotic drugs were associated with increased risks of mortality and cancer, including the popularly prescribed medications zolpidem (best known by the brand name Ambien), temazepam (Restoril) and eszopiclone (Lunesta).

The other five drugs or drug groups analyzed were: zaleplon (Sonata); triazolam (Halcion); the group flurazepam, quazepam and estazolam considered together; barbiturates, mainly phenobarbital; and antihistamines, mainly diphenhydramine (Benadryl, Sominex), when used for sleep.

These newer sleeping aids, often referred to collectively as sedative-hypnotic drugs or hypnotics, had been thought to be safer than older sleeping pills because of their shorter duration of action.

The study included 10,531 sleeping pill users who were prescribed the medications for an average of 2.5 years and 23,674 control participants who were not prescribed the drugs. Information came from outpatient clinic visits conducted between Jan. 1, 2002, and Sept. 30, 2006.

During the 4½ years of the study, rates of new cancers were 35 percent higher among patients who were prescribed at least 132 hypnotic doses a year as compared with those who did not take the drugs.

Even among patients who were prescribed just one to 18 sleeping pills per year, the risk of death was 3.6 times higher than among similar participants who did not take the medications. The study looked at patients 18 and older, and found the increased risk in all age groups.

There are no studies showing that the higher mortality risk would be immediately reduced if people quit taking the drugs, but Kripke said he “would guess that the risk would go down when they stop.”

“It is important to note that our results are based on observational data, so even though we did everything we could to ensure their validity, it’s still possible that other factors explain the associations,” said co-author Dr. Lawrence E. Kline, medical director of the Scripps Clinic Viterbi Family Sleep Center.

In a statement, Sunovion Pharmaceuticals, the maker of Lunesta, said its sleeping pill has been shown to be safe and effective.

“Lunesta has been extensively studied in multiple clinical trials including a six-month double-blind, placebo-controlled trial to assess long-term safety and efficacy,” said Dr. Fred Grossman, senior vice president of clinical development and medical affairs at the Massachusetts company. “In that trial, as in other published eszopiclone clinical trials, it was shown that the effects on mortality were not different between the Lunesta and placebo groups.”

Sanofi, maker of Ambien, said in a statement that it believes the limitations of the analysis and conclusions based on the data presented make the study “highly questionable.”

“Ambien has more than 17 years of real-world experience and is safe and effective when prescribed and taken according to its labeling,” the Paris-based pharmaceutical company said.

The study, which was funded by Scripps Health Foundation and philanthropic sources, received mostly positive reviews from San Diego sleep specialists.

“I realize they can’t do a controlled study for something like this, but this study is about as close to one as I’ve seen,” said Dr. Larry Ayers, director of the Sharp Grossmont Hospital Sleep Center. “I think this shows a real strong relationship between using sleeping pills and increased mortality.”

Although sleep researcher Carl Stepnowsky, an assistant adjunct professor at University of California San Diego Medical Center, thought the study was “particularly well done,” he had concerns that it was based on retrospective data from medical records.

“We know the drugs were ordered, but we don’t know for sure that people took them,” he said. “I do a lot of treatment adherence research, and the adherence rate is about 50 percent for medications.”

Palomar Pomerado Health sleep specialist Dr. Richard Schumann said he thought the study was “fair and balanced,” but said he found it “difficult to make the leap that these drugs caused the deaths based on this report.”

The one point that all agreed on was that sleeping pills are overprescribed and can be problematic, especially when used long term.

“Physicians are not screening the appropriateness of use of these sleeping pills. These drugs were not designed for long-term use,” Schumann said. “Patients end up depending on them so they end up not only having a sleep problem but they also have a dependence problem.”

The prescription sleep aid industry has grown by 23 percent in the United States from 2006 to 2010, generating about $2 billion in annual sales.

The National Center of Sleep Disorders Research at the National Institutes of Health estimates that 30 percent to 40 percent of adults have some symptoms of insomnia in a given year and as many as 15 percent have chronic insomnia.

All the sleep specialists interviewed said that using cognitive behavioral therapy and practicing good sleep habits is a safer and more effective treatment for insomnia than sleeping pills.